| Project/Area Number |
02454242
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
TAKAGI Kenzo (1991) Nagoya Univ. School of Med., assistant professor, 医学部, 講師 (50093050)
佐竹 辰夫 (1990) 名古屋大学, 医学部, 教授 (60023743)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Kenji Aichi Medical University assistant professor, 医学部, 講師 (80211499)
YAMAKI Kenichi Nagoya Univ. School of Med. Assistant, 医学部, 助手 (20182420)
高木 健三 名古屋大学, 医学部, 講師 (50093050)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1990: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Asthma attack / Phosphatidylinosides / GTP-binding protein / Phospholipase A2 / Protein kinase C / Neuropeptide / Ca channel / Histamine / フォスフォライペ-スA_2 / Caチャネル / 気管支喘息 / Phospholipase A_2 / Interleukinー2 / Interferonーα / superoxide production / inflammatory lipids / Priming effect |
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| Research Abstract |
To elucidate the functions of phosphatidylinosides-Ca^<2+> system in asthma attack in patients with bronchial asthma, and physiological, biochemical and pharmacological approaches were performed in this study. In this study using swine tracheal smooth muscle, it was found that phorbol ester which activated protein kinase C, evoked large increases of Ca influx even at small membrane depolarization by contractile agonists that function through receptor activations. It is known that contractile agonists through receptor activations stimulate inositol phospholipid metabolisms in airway smooth muscle cells, resulting in the production of inositol trisphosphate and diacylglycerol which activates protein kinase C. Thus, it is concluded that the responses to slower concentrations of histamine in the presence of the three agonists (PGF, carbachol and serotonin) is mainly dependent on the influx of external Ca and that the agonists-induced activaton of protein kinase C as well as membrane depolarization may be responsible for the increase of the histamine-induced Ca influx, eventually enhancing the histamine contractions.
In addition, we showed that both forms of PACAP tested may act as novel potent relaxants on tracheal smooth muscle by raising tissue cyclic AMP levels and membrane-binding phospholipase A2 activity of PMN would thus appea to be regulated directly by GTP-binding protein.
We should try on next steps to elucidate the functions of inositol triphosphate-Ca^<2+> system in bronchial asthma.
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